The sequences of 6000 genes representing the complete genome of Saccharomyces cerevisiae (the budding yeast) will be available by 1997. As a "model" eukaryotic organism, this data will represent a resource of enormous value for interpreting human genes as has been dramatically demonstrated in the past year by the isolation of several DNA mismatch repair genes that are responsible for the pathophysiology of colon carcinoma. We have been awarded a grant from the National Center for Human Genome Research to systematically search for new yeast-human homologue pairs in the expanding human EST data (see Z0l-LM-000l5-02-CBB) and to map approximately 1,000 of these to mouse and human chromosomes. We expect to find a number of yeast proteins that will become models for human disease genes by virtue of their map locations.